This proposal is for the competitive renewal of RO1 AG06537, which is in its 14th consecutive year of funding. Since 1990 the focus of the research has been the effects of primary human aging on autonomic nervous system (ANS), particularly sympathetic nervous system (SNS), behavior. We propose to extend our previous findings by determining: a) the physiological significance of age-related changes in ANS behavior; b) age- gender interactions; and c) if habitual exercise can reverse or at least attenuate some of the potentially adverse physiological events associated with these age-related ANS adaptations. The following hypotheses will be tested: 1) ANS "support" of arterial blood pressure (BP) will increase progressively with advancing age, but will be smaller in adult females than males of the same age; 2) these age and gender effects will be associated primarily with differences in the regulation of heart rate and cardiac output, rather than systemic vascular conductance; 3) systemic and limb arterial vascular responsiveness to alpha- and beta- adrenergic stimulation, and cardiac chronotropic responsiveness to beta-adrenergic stimulation, will be attenuated progressively with age; women will demonstrate smaller vascular responsiveness than men of similar age; 4) SNS beta-adrenergic support of resting metabolic rate (RMR) will decrease progressively with advancing age, and adult females will demonstrate less SNS beta- adrenergic support of RMR than males of the same age; 5) the declines in systemic and limb arterial vascular responsiveness to alpha-and beta-adrenergic stimulation and SNS beta-adrenergic support of RMR with age in sedentary adults either will be absent or attenuated in men and women who habitually perform aerobic- endurance exercise; and 6) the age-associated loss of vascular responsiveness to alpha- and beta-adrenergic stimulation and SNS beta-adrenergic support of RMR will be restored completely or in part by a program of moderate regular aerobic-endurance exercise in previously sedentary middle-aged and older adults. After extensive screening to establish eligibility, sedentary and endurance exercise-trained healthy men and women aged 18-30 (young adults), 40-55 (middle-aged), and 65-79 (older) years will be studied under well-controlled experimental conditions. To address Specific Aim 6, 40 previously sedentary middle-aged and older men and women will participate in a 3-month aerobic- endurance exercise intervention with a waiting list time control. The proposed studies should provide new, clinically relevant insight into the links between age- and gender-associated changes in ANS and SNS behavior and physiological function, as well as the potentially favorable modulatory effects of regular exercise.